Abstract
Introduction: Neovascularization of the fracture site is of great importance for bone healing and could be influenced by local mechanical environment such as fixation stability and inter-fragmentary gap size. This study aims to reconstruct the neovascularization of the fracture site and explore the effect of inter-fragmentary gap size on the spatiotemporal structure of vascularity during bone healing. Methods: Osteotomy was performed on 36 Sprague–Dawley (SD) rats on the right tibial diaphysis, and the fracture was given stable fixation with two different inter-fragmentary gap sizes. SD rats received stable fixation with either a small-sized inter-fragmentary gap (FSF1, 1 mm, n = 18) or a large-sized one (FSF3, 3 mm, n = 18). The left hind limbs were treated as the control group (CON). The animals were killed at different time points (2, 4, and 6 weeks postoperatively, n = 6, respectively) for vascular perfusion and micro-CT imaging. Results: (a) At week 2 and 4, FSF1 group showed significantly higher vessel volume ratio (VV/TV) and vessel surface density (VS/TV) values than both CON and FSF3 group; there was no significant difference in either VV/TV or VS/TV values between CON and FSF3 groups. (b) At week 6, both FSF1 and FSF3 groups showed significantly higher VV/TV and VS/TV values than CON group; FSF3 group had a significantly higher VV/TV value than FSF1 group. Conclusion: Different inter-fragmentary gap sizes greatly affect the timing of angiogenesis at the fracture site. Stable fixation with a small inter-fragmentary gap (1 mm) benefits neovascularization at the early stages during bone healing and reconstruction, while stable fixation with a large inter-fragmentary gap (3 mm) delays the occurrence of angiogenesis to a later phase.
Highlights
Neovascularization of the fracture site is of great importance for bone healing and could be influenced by local mechanical environment such as fixation stability and inter-fragmentary gap size
At week 6, FSF3 specimens displayed a larger number of microvessels than the FSF1 group
From the numerical values such as vessel volume ratio (VV/ TV) and vessel surface density (VS/TV) calculated from the micro-CT images, we found that the FSF1 group had more vessels visually and significantly higher VV/TV and VS/TV values than the control group (CON) group at all sacrifice times; and at weeks 2 and 4, the FSF1 group had more vessels visually and a significantly higher VV/TV value than the FSF3 group (Week 2: VV/TVFSF1 = 1.59 ± 0.53% > VV/TVFSF3 = 1.18 ± 0.24%, p < 0.05; Week 4: VV/TVFSF1 = 1.68 ± 0.24% > VV/TVFSF3 = 1.18 ± 0.16%, p < 0.01)
Summary
Neovascularization of the fracture site is of great importance for bone healing and could be influenced by local mechanical environment such as fixation stability and inter-fragmentary gap size. Bone fracture healing is a sophisticated physiological process, results of which mainly depend on blood supply (Glowacki, 1998; Carano and Filvaroff, 2003; Tomlinson et al, 2013) and local mechanical environment (Bailón-Plaza and van der Meulen, 2003; Gardner and Mishra, 2003; Epari et al, 2010) of the fracture site. It was demonstrated that bone healing was prevented in a murine fracture model receiving angiogenesis inhibitors (Hausman et al, 2001) In another murine osteotomy model, local inhibition of angiogenesis was shown to result in an atrophic non-union (Fassbender et al, 2011)
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